甲状腺激素与特发性肺纤维化相关性的研究进展

特发性肺纤维化(IPF)是一种病因不明的慢性进行性疾病,以肺实质瘢痕形成为特征,导致生活质量降低和过早死亡。目前有研究证实甲状腺功能减退症(HT)可能在纤维化的发展中发挥作用,多个动物实验证明甲状腺激素(TH)可通过调节糖代谢、改善线粒体功能、抑制炎症等途径抑制肺纤维化。本文就TH与IPF的相关性进行总结,深入认识二者关系,以期未来IPF有新的治疗策略。     

喘可治和香菇多糖注射液在细胞和荷瘤裸鼠水平增效紫杉醇的抗肿瘤作用研究

目的测试喘可治与香菇多糖注射液对紫杉醇的肿瘤化疗作用是否具有增效影响。方法肿瘤细胞经紫杉醇单独,或联合无细胞毒浓度的喘可治、低细胞毒浓度的香菇多糖作用48 h或72 h后,MTT法测定细胞的相对活力;荷瘤裸鼠分别采用紫杉醇、喘可治、香菇多糖、紫杉醇联合喘可治、紫杉醇联合香菇多糖治疗10 d,观察肿瘤的生长情况。结果喘可治注射液8倍以内的稀释液,或者60~1000μg·m L~(-1)浓度的香菇多糖对人口腔上皮癌细胞株KB-3-1、人宫颈癌细胞株He La的增殖具有明显的抑制作用。喘可治注射液稀释16~30倍对KB-3-1和He La细胞不产生细胞毒作用,但与紫杉醇联用能增强后者的细胞毒作用;无毒浓度香菇多糖(30μg·m L~(-1))与紫杉醇联用不增强紫杉醇的细胞毒活性,低毒浓度的香菇多糖(60、90μg·m L~(-1))与紫杉醇联合的效果则表现为加和性。喘可治或香菇多糖与紫杉醇联用,均能够显著增强化疗药物对裸鼠负荷的KB-3-1移植瘤生长的抑制作用,显著改善紫杉醇造成的小鼠体重减轻。结论喘可治和香菇多糖注射液与紫杉醇联用获得更好的体内外抗肿瘤效果,喘可治或香菇多糖注射液与紫杉醇联合用药有益于癌症的治疗。     

喘可治注射液不同给药途径治疗婴幼儿毛细支气管炎临床疗效比较

目的 探讨喘可治注射液两种给药方式治疗婴幼儿毛细支气管炎的临床疗效对比。方法 将179例毛细支气管炎患儿随机分为两组,在常规对症支持治疗的基础上,观察组氧气驱动雾化吸入0.9%氯化钠溶液2ml+喘可治注射液1ml,对照组给药喘可治注射液1ml肌肉注射,观察两组患者临床疗效。结果 临床总有效率为观察组95.6%,对照组85.9%,差异显著,具有统计学意义(P<0.05);观察组患者咳嗽和双肺干湿性啰音消失时间及平均住院时间皆少于对照组,两组差异性显著(P<0.05)。结论 喘可治注射液两种不同的给药途径均是治疗婴幼儿毛细支气管炎的有效方法,但喘可治注射液雾化吸入疗效优于肌肉注射,而且安全有效,患儿易于接受,值得在儿科临床推广应用。     

喘可治注射液辅助治疗慢性支气管炎52例疗效观察

喘可治注射液（以下简称喘可治）具有温阳补肾、平喘止咳的作用,可用于治疗慢性支气管炎。我院应用喘可治联合阿奇霉素治疗老年慢性支气管炎52例,疗效显著,现报告如下。     

喘可治注射液治疗支气管哮喘疗效观察

目的 探讨喘可治注射液治疗支气管哮喘临床疗效。方法 56例支气管哮喘患者按随机数字表法随机分为治疗组和对照组,各28例。对照组采用常规治疗,治疗组在此基础上采用喘可治注射液雾化吸入,两组均治疗14 d,观察疗效。结果 治疗组总有效率为96.4%,对照组总有效率为82.1%,治疗组疗效及肺功能改善均优于对照组,差异具有统计学意义(P<0.05)。结论 雾化吸入喘可治注射液治疗支气管哮喘疗效确切,安全可靠,值得推广应用。     

喘可治注射液治疗哮喘的疗效及其作用机制研究

目的: 评价喘可治注射液治疗哮喘的有效性、安全性及作用机制。方法: 62例哮喘病人分 2组,喘可治组使用喘可治注射液 (4mL·次 -1,qd),对照组使用相同剂量的安慰剂;疗程共 4wk。2组病人治疗前后行肝、肾功能,血、尿常规,心电图及细胞因子检测。结果:治疗后 2组日间症状评分(1. 30±s0. 20)分vs(0. 50±0. 10)分、夜间憋醒次数(1. 10±0. 20)次vs(0. 40±0. 20 )次及沙丁胺醇减少喷数(1. 40±0. 20)次vs(0. 60±0. 10 )次比较,差异有非常显著意义(P<0. 01); 2组肺功能较治疗前均有非常显著改善 (P<0. 01); 2组组间比较,差异亦有非常显著意义(P<0. 01)。治疗后 2组病人血常规,肝、肾功能及心电图无明显异常。喘可治组使Th1 /Th2细胞因子比值提高 15. 3±1. 3,对照组仅提高 9. 2±1. 0, 2组比较差异有非常显著意义 (P<0.01)。结论 :喘可治注射液是治疗哮喘有效、安全的中药制剂,它可能是通过调整Th1 /Th2平衡发挥疗效的。     

喘可治注射液雾化吸入给药对豚鼠肺指数及气管、肺、食管组织形态学的影响

目的:观察喘可治注射液雾化吸入给药对豚鼠肺指数及气管、食管等器官组织形态学的影响。方法:将40只豚鼠随机均分为空白对照组(生理盐水)和喘可治高、中、低(2.48、1.24、0.62 ml/kg)剂量组,雾化喷雾吸入给药,20 ml/kg,每天1次,连续给药2周。每次给药1 h后观察豚鼠一般情况;末次给药1 h后检测豚鼠肺指数,并采用苏木精-伊红(HE)染色观察豚鼠左肺、右肺、气管及食管的组织形态学变化。结果:与正常对照组比,喘可治高、中、低剂量组豚鼠的一般情况均正常;肺指数无差异,均为0.653左右;组织切片染色结果显示各组织未见异常病变。结论:喘可治注射液雾化吸入给药2周对豚鼠肺指数及气管、肺、食管等器官组织形态学无明显影响。     

心喘灵(XC-1)及其衍生物XC-2对麻醉犬血流动力学的作用

本工作比较研究了心喘灵(XC-1)及其衍生物XC-2(8204) 对麻醉开胸犬心脏血流动力学的作用。用递加剂量法静注心喘灵0.5,1.0,2.0和4.0 mg/kg,每二个剂量之间的间隔为5 min,给药后MAP和LVP下降,HR减慢,CI和SI增加,TPR降低,冠状、颈内和股动脉血流增加,血管阻力下降,±LVdp/dt max增加,而LV dp/dt/p改变不明显,LVW,CVP和MVO₂无明显变化。用同法静注同样剂量XC-2的作用和心喘灵相似,但较弱;一次静注5 mg/kg也出现柑似但较弱的作用。它们的作用是通过阻断α和β受体及直接扩张血管所引起。     

硫酸镁静滴联合喘可治雾化吸入治疗儿童喘息样支气管炎的临床分析

目的探讨硫酸镁静滴联合喘可治雾化吸入治疗儿童喘息样支气管炎的临床疗效。方法选择急性喘息性支气管炎及哮喘急性发作的患儿84例,将患儿分为治疗组(42例)和对照组(42例),其中治疗组在常规治疗的同时使用喘可治加硫酸镁静脉输入,对照组常规治疗的同时采用抗病毒、雾化吸入,若有合并感染者加用抗生素等方法进行治疗。观察治疗前后患儿的咳嗽、气喘改善情况。结果治疗组的患儿临床症状改善情况明显优于对照组(P<0.05)。结论硫酸镁静滴联合喘可治雾化吸入治疗儿童喘息性支气管炎效果明显,可提高疗效。     

喘可治注射液雾化吸入佐治小儿喘息性支气管炎45例疗效观察

目的观察喘可治注射液雾化吸入佐治小儿喘息性支气管炎临床疗效。方法将90例患儿随机分为治疗组与对照组各45例,对照组采用沐舒坦注射液雾化吸入,治疗组用喘可治注射液雾化吸入。结果治疗组治愈率75.56%,对照组为48.89%,治疗组在平喘,肺部啰音消失时间及减少复发次数方面明显优于对照组,两组比较差异有显著性意义(P<0.05)。结论喘可治注射液雾化吸入佐治小儿喘息性支气管炎可明显提高疗效。     

Theoretical π-π* absorption and circular dichroic spectra of cyclic dipeptides

The dipole interaction model, treated by the partially dispersive normal mode method, is used to calculate circular dichroic spectra of cyclo(Gly-Gly), cyclo (Ala-Gly), cyclo(Ala-Ala), cyclo(Pro-Gly), cyclo(Pro-Ala), cyclo(Pro-Val), cyclo (Pro-D-Val), and cyclo(Pro-Pro) in the amide π-π* absorption band near 190 nm. Assuming a standard backbone geometry, spectra which are in fair to good agreement wth experiment are obtained for these molecules. The spectra are predicted to be sensitive to conformations of Pro and Val side chains. The effects of dipeptide ring folding on calculated CD spectra are mostly consistent with those found by other workers, except that it is found that a planar ring conformation of cyclo (Ala-Ala) and cyclo (Ala-Gly) gives predicted spectra comparable to experiment. The same model gives theoretical absorption spectra consistent with available experimental data.     

Effects of Nitro-L-Arginine on Blood Pressure and Cardiac Index in Anesthetized Rats: A Pharmacokinetic-Pharmacodynamic Analysis

Purpose. Nitric oxide synthase (NOS) inhibitors such as Nitro-L-arginine (L-NA) are being considered for the management of hypotension observed in septic shock. However, little information is available regarding the pharmacokinetic and pharmacodynamic properties of these agents. Our objective was to examine the relationships between L-NA plasma concentration and various hemodynamic effects such as cardiac index (CI), mean arterial pressure (MAP), and heart rate (HR) elicited by L-NA administration in rats. Methods. L-NA was infused at doses between 2.5 – 20 mg/kg/hr in anesthetized rats over one hour. Hemodynamic effects and plasma L-NA levels were determined. Results. Infusion of L-NA resulted in dose-dependent increases in MAP and systemic vascular resistance (SVR), decreases in CI, and minimal change in HR. The relationships between the hemodynamic effects and plasma L-NA levels were not monotonic, and hysteresis was observed. Using nonparametric analysis, the equilibration half-time (t_1/2,keo) between plasma L-NA and the hypothetical effect site was determined to be 51.5 ± 6.6 min, 42.4 ± 10.1 min, 43.4 ± 9.0 min for MAP, CI, and SVR, respectively (n = 14). The E_max and EC₅₀ values obtained were + 32.5 ± 8.4 and 2.6 ± 1.3 g/ml for MAP and –52.9 ± 15.6 and 3.7 ± 1.8 g/ml for CI, respectively. Conclusions. Although L-NA can bring about beneficial elevation of MAP, such effect is always accompanied by a stronger effect on CI depression. Dose escalation of L-NA may bring about detrimental negative inotropic effect and loss of therapeutic efficacy.     

洛美沙星体内外抗菌活性研究

洛美沙星对革兰氏阴性菌具有强的抑菌活力。对克氏肺炎杆菌的抗菌活性最强,MIC_(50)为0.12mg/L;对痢疾杆菌、产气杆菌、粘质沙雷氏菌、不动杆菌和枸椽酸杆菌的MIC_(50)分别为1和4mg/L。洛美沙星对肠细菌科细菌的活力比诺氟沙星和依诺沙星强2～16倍,明显地比丁胺卡那霉素、庆大霉素强。对金葡球菌MIC_(50)为1mg/L, MRSA对洛美沙星同样敏感。洛美沙星对表葡球菌、链球菌、粪链球菌及肺炎双球菌等的抗菌活性与地氟沙星相似,比诺氟沙星、依诺沙星、丁胺卡那霉素、庆大霉素和头孢三嗪分别强2～4倍。 洛美沙星对小鼠全身感染的疗效优于诺氟沙星。对大肠杆菌、克氏肺炎杆菌和绿脓杆菌感染小鼠iv的ED_(50)分别是0.74、0.13和3.45mg/kg, po的ED_(50)分别是0.94、1.46和6.20mg/kg。     

乙酰吉他霉素临床前药理学研究

乙酰吉他霉素对临床分离的革兰氏阳性球菌有较好的抑菌活力，其对金葡球菌、β－溶血性链球菌、表葡球菌的ＭＩＣ_（５０）分别为１、０．２２和４ｍｇ／Ｌ，对耐红霉素、青霉素的金葡球菌、表葡球菌半数以上较敏感，与吉他霉素相似，但其对革兰氏阴性菌无明显作用。乙酰吉他霉素对小鼠实验性细菌感染有明显保护作用。对金葡球菌、肺炎双球菌感染小鼠口服用药的ＥＤ_（５０）分别为７９．６和２５．１ｍｇ／ｋｇ。其疗效与吉他霉素、麦白霉素、乙酰螺旋霉素相似。乙酰吉他霉素小鼠１次口服的ＬＤ_（５０）＞１５ｇ／ｋｇ，与吉他霉素相比毒性无差异。     

HPLC法测定丝裂霉素C聚氰基丙烯酸正丁酯纳米粒中丝裂霉素C的含量

目的:建立高效液相色谱法测定丝裂霉素 C 聚氰基丙烯酸正丁酯纳米粒(MMC-PBCA-NP)中药物含量。方法:采用C_(18)柱(4.6 mm×150 mm,5 μm),以混合磷酸盐缓冲液-乙腈(85:15)为流动相,流速为1 mL·min~(-1),紫外检测器,检测波长为365 nm。结果:丝裂霉素 C(MMC)浓度在5～250 μg·mL~(-1)范围内与峰面积呈良好的线性关系,r=0.9998;平均回收率(n=6)为98.15%。结论:本法专属性强,操作简便,结果准确。适用于 MMC-PBCA-NP 的质量控制。     

The pathogenesis of,and pharmacological treatment for,Canavan disease

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大鼠溃疡性结肠炎模型的实验研究

目的对不同剂量的三硝基苯磺酸（ＴＮＢＳ）引起的大鼠溃疡性结肠炎（ＵＣ）模型进行观察和评价。方法采用一次性直肠注入大鼠ＴＮＢＳ（２５～１５０ｍｇ·ｋｇ－１）的３０％乙醇溶液，引起慢性炎症性肠疾病（ＩＢＤ），３ｗｋ后外死动物对各剂量下动物结肠的重量、髓过氧化物酶（ＭＰＯ）活性及组织形态学变化进行观察和评价。结果ＴＮＢＳ在１００～１５０ｍｇ·ｋｇ－１剂量下引起的ＵＣ肠壁明显增厚，炎症和溃疡至少维持７ｗｋ时间，ＭＰＯ活性值显著性升高，组织学检查发现粘膜及粘膜下层有大量中性粒细胞及淋巴细胞、巨噬细胞、纤维细胞浸润，肉芽组织及隐窝脓肿形成，５０ｍｇ·ｋｇ－１剂量时有一较轻度的损伤。２５ｍｇ·ｋｇ－１时对结肠的重量、ＭＰＯ活性及损伤指数都没有显著性改变（Ｐ＞０．０５）。结论用ＴＮＢＳ引起大鼠实验性ＵＣ，其溃疡和炎症维持一较长时间，这一病理特征为炎症性疾病防治药物的研究提供了条件；本模型的最佳剂量为１００ｍｇ·ｋｇ－１左右     

Protective role of exogenous α-lipoic acid (ALA) on hippocampal antioxidant status and memory function in rat pups exposed to sodium arsenite during the early post-natal period

The present work focussed on the effect of exogenous α-lipoic acid (ALA) administration on retention memory and oxidative stress markers in the hippocampus subsequent to early post-natal exposure of rat pups to sodium arsenite (NaAsO₂). Wistar rat pups were divided into the control groups receiving either no treatment (Ia) or distilled water by intraperitoneal route (i.p.) (Ib) and the experimental groups receiving either NaAsO₂ alone (1.5 and 2.0?mg/kg body wt.) (IIa, IIb) or NaAsO₂ (1.5 and 2.0?mg/kg body wt.) followed by ALA (70?mg/kg body wt.) (IIIa, IIIb) (i.p.) from post-natal day (PND) 4–15. The initial and retention transfer latency (ITL and RTL) was determined on PND 14 and 15 using elevated plus maze. The animals were sacrificed by cervical decapitation (PND 16) and the brains were obtained. The dissected out hippocampus was processed for estimation of oxidative stress markers, glutathione (GSH), and superoxide dismutase (SOD). NaAsO₂ exposure resulted in longer RTL in animal groups IIa and IIb, thereby suggestive of arsenic-induced impairment in retention memory. RTL was significantly shorter in animal groups (IIIa, IIIb) receiving ALA following NaAsO₂, thereby suggestive of improvement in retention memory. GSH and SOD levels were significantly decreased in animals receiving NaAsO₂ alone as against group Ib and administration of ALA following NaAsO₂ increased the levels of hippocampal GSH and SOD. These observations are suggestive of the role of exogenous ALA in ameliorating the adverse effects induced by NaAsO₂ exposure of rat pups on retention memory and oxidative stress markers.     

Dinoflagellate polyether within the yessotoxin, pectenotoxin and okadaic acid toxin groups: Characterization, analysis and human health implications

Diarrhetic Shellfish Poisoning (DSP) is a specific type of food poisoning, characterized by severe gastrointestinal illness due to the ingestion of filter feeding bivalves contaminated with a specific suite of toxins. It is known that the problem is worldwide and three chemically different groups of toxins have been historically associated with DSP syndrome: okadaic acid (OA) and dinophysistoxins (DTXs), pectenotoxins (PTXs) and yessotoxins (YTXs). PTXs and YTXs have been considered as DSP toxins because they can be detected with the bioassays used for the toxins of the okadaic acid group, but diarrhegenic effects have only been proven for OA and DTXs. Whereas, some PTXs causes liver necrosis and YTXs damages cardiac muscle after intraperitoneal injection into mice. On the other hand, azaspiracids (AZAs) have never been included in the DSP group, but they cause diarrhoea in humans. This review summarizes the origin, characterization, structure, activity, mechanism of action, clinical symptoms, method for analysis, potential risk, regulation and perspectives of DSP and associated toxins produced by marine dinoflagellates.     

Latent role of in vitro Pb exposure in blocking Aβ clearance and triggering epigenetic modifications

Both β-amyloid (Aβ) catabolism and epigenetic regulation play critical roles in the onset of neurodegeneration. The latter also contribute to Pb neurotoxicity. The present study explored the role of epigenetic modifiers and Aβ degradation enzymes in Pb-induced latent effects on Aβ overproduction in vitro. Our results indicated that in SH-SY5Y cells exposed to Pb, the expression of NEP and IDE remained declined during the recovery period, accompanied with abnormal increase of Aβ_1-42 and amyloid oligomer. A disruption of selective global post-translational histone modifiers including the decrease of H3K9ac and H4K12ac and the induction of H3K9me2 and H3K27me2 dose dependently was also showed in recovery cells. Moreover, histone deacetylase inhibitor VPA could attenuate latent Aβ accumulation and HDAC activity induced by Pb, which might be by regulating the expression of NEP and IDE epigenetically. Overall, our results suggest sustained reduction of NEP and IDE expression in response to Pb sensitizes recovery SH-SY5Y cells to Aβ accumulation; however, administration of VPA is demonstrated to be beneficial in modulating Aβ clearance.